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    Partially deglycosylated glucocerebrosidase polypeptide and crystals thereof
    3.
    发明授权
    Partially deglycosylated glucocerebrosidase polypeptide and crystals thereof 失效
    部分去糖基化的葡萄糖脑苷脂酶多肽及其晶体

    公开(公告)号：US07855063B2

    公开(公告)日：2010-12-21

    申请号：US10552287

    申请日：2004-04-18

    申请人： Anthony Futerman ,  Joel L. Sussman ,  Israel Silman ,  Michal Harel ,  Hay Dvir ,  Lilly Toker

    发明人： Anthony Futerman ,  Joel L. Sussman ,  Israel Silman ,  Michal Harel ,  Hay Dvir ,  Lilly Toker

    IPC分类号： C12N9/26 ,  A61K38/47

    CPC分类号： A61K38/47 ,  C12N9/2402 ,  C12Y302/01045 ,  C12Y305/01052 ,  G01N33/573 ,  G01N2500/04

    摘要： A method of identifying a compound capable of correcting an impaired enzymatic activity of a mutant glucocerebrosidase molecule, the method comprising: (a) obtaining a first set of structure coordinates, the first set of structure coordinates defining a 3D structure of a glucocerebrosidase molecule capable of displaying normal enzymatic activity or a portion thereof; (b) computationally generating using the first set of structure coordinates a second set of structure coordinates, the second set of structure coordinates defining a predicted 3D structure of the mutant glucocerebrosidase molecule or a portion thereof; and (c) computationally identifying, using the second set of structure coordinates, a compound capable of interacting with the mutant glucocerebrosidase molecule in such a way as to correct the impaired enzymatic activity thereof, thereby identifying the compound capable of correcting the impaired enzymatic activity of the mutant glucocerebrosidase molecule. A glucocerebrosidase preparation comprising a population of glucocerebrosidase molecules, wherein substantially each of said glucocerebrosidase molecules: (i) has an amino acid sequence at least 95 percent homologous to an amino acid sequence set forth by SEQ ID NO: 1 or 8; (ii) is glycosylated at, or has an aspartatic acid residue at, glycosylation residue 1 of said amino acid sequence; and (iii) is independently unglycosylated at one or more glycosylation residues selected from the group consisting of glycosylation residues 2, 3 and 4 of said amino acid sequence.

    摘要翻译： 一种鉴定能够校正突变型葡糖脑苷脂酶分子受损的酶活性的化合物的方法，所述方法包括：（a）获得第一组结构坐标，所述第一组结构坐标定义了能够产生以下结构的葡萄糖脑苷脂酶分子的3D结构 显示正常的酶活性或其一部分; （b）使用所述第一组结构坐标计算生成第二组结构坐标，所述第二组结构坐标定义所述突变型葡糖脑苷脂酶分子或其部分的预测3D结构; 和（c）使用第二组结构坐标计算地鉴定能够与突变型葡糖脑苷脂酶分子相互作用的化合物，以便校正受损的酶活性，从而鉴定能够校正受损的酶活性的化合物 突变型葡糖脑苷脂酶分子。 包含一群葡萄糖脑苷脂酶分子的葡糖脑苷脂酶制剂，其中基本上每一种所述的葡糖脑苷脂酶分子：（i）具有与SEQ ID NO：1或8所示的氨基酸序列至少95％同源的氨基酸序列; （ii）在所述氨基酸序列的糖基化残基1处糖基化，或具有天冬氨酸残基; 和（iii）在选自所述氨基酸序列的糖基化残基2,3和4的一个或多个糖基化残基处独立地未糖基化。

    Gaucher disease drugs and methods of identifying same
    4.
    发明申请
    Gaucher disease drugs and methods of identifying same 失效
    戈谢病药物及其鉴别方法

    公开(公告)号：US20070166813A1

    公开(公告)日：2007-07-19

    申请号：US10552287

    申请日：2004-04-18

    申请人： Anthony Futerman ,  Joel Sussman ,  Israel Silman ,  Michal Harel ,  Hay Dvir ,  Lilly Toker ,  Swetlana Adamsky

    发明人： Anthony Futerman ,  Joel Sussman ,  Israel Silman ,  Michal Harel ,  Hay Dvir ,  Lilly Toker ,  Swetlana Adamsky

    IPC分类号： C12N9/24 ,  G06F19/00

    CPC分类号： A61K38/47 ,  C12N9/2402 ,  C12Y302/01045 ,  C12Y305/01052 ,  G01N33/573 ,  G01N2500/04

    摘要： A method of identifying a compound capable of correcting an impaired enzymatic activity of a mutant glucocerebrosidase molecule, the method comprising: (a) obtaining a first set of structure coordinates, the first set of structure coordinates defining a 3D structure of a glucocerebrosidase molecule capable of displaying normal enzymatic activity or a portion thereof; (b) computationally generating using the first set of structure coordinates a second set of structure coordinates, the second set of structure coordinates defining a predicted 3D structure of the mutant glucocerebrosidase molecule or a portion thereof; and (c) computationally identifying, using the second set of structure coordinates, a compound capable of interacting with the mutant glucocerebrosidase molecule in such a way as to correct the impaired enzymatic activity thereof, thereby identifying the compound capable of correcting the impaired enzymatic activity of the mutant glucocerebrosidase molecule. A glucocerebrosidase preparation comprising a population of glucocerebrosidase molecules, wherein substantially each of said glucocerebrosidase molecules: (i) has an amino acid sequence at least 95 percent homologous to an amino acid sequence set forth by SEQ ID NO: 1 or 8; (ii) is glycosylated at, or has an aspartatic acid residue at, glycosylation residue 1 of said amino acid sequence; and (iii) is independently unglycosylated at one or more glycosylation residues selected from the group consisting of glycosylation residues 2, 3 and 4 of said amino acid sequence.

    摘要翻译： 一种鉴定能够校正突变型葡糖脑苷脂酶分子受损的酶活性的化合物的方法，所述方法包括：（a）获得第一组结构坐标，所述第一组结构坐标定义了能够产生以下结构的葡萄糖脑苷脂酶分子的3D结构 显示正常的酶活性或其一部分; （b）使用所述第一组结构坐标计算生成第二组结构坐标，所述第二组结构坐标定义所述突变型葡糖脑苷脂酶分子或其部分的预测3D结构; 和（c）使用第二组结构坐标计算地鉴定能够与突变型葡糖脑苷脂酶分子相互作用的化合物，以便校正受损的酶活性，从而鉴定能够校正受损的酶活性的化合物 突变型葡糖脑苷脂酶分子。 包含一群葡萄糖脑苷脂酶分子的葡糖脑苷脂酶制剂，其中基本上每一种所述的葡糖脑苷脂酶分子：（i）具有与SEQ ID NO：1或8所示的氨基酸序列至少95％同源的氨基酸序列; （ii）在所述氨基酸序列的糖基化残基1处糖基化，或具有天冬氨酸残基; 和（iii）在选自所述氨基酸序列的糖基化残基2,3和4的一个或多个糖基化残基处独立地未糖基化。